Strategy for 14C‐labeling of a series of bis(heteroaryl)piperazines

Four bis(heteroaryl)piperazines labeled with carbon‐14 in the 2‐position of imidazole moiety were prepared as part of a 4‐step (or 5‐step) sequence from 5‐hydroxymethyl‐2‐mercapto‐1‐benzylimida‐zole‐[2‐¹⁴C] as a key synthetic intermediate which has been synthesized from potassium [¹⁴C]‐thiocyanate. Copyright © 2011 John Wiley & Sons, Ltd.     

Pre‐medication and renal pre‐conditioning: a role for alprazolam,atropine, morphine and promethazine

Four pre‐medication drugs are used to relieve pain, allay anxiety, reduce secretion and enhance hypnosis, were evaluated for their effects on ischemia reperfusion (I/R) injury which is one of the major complications of vascular and transplantation surgery. Right kidney was removed from female rats (210–250 g) 3 weeks before surgical procedure. Different doses of morphine (0.5, 2 and 5 mg/kg), promethazine (1, 2 and 5 mg/kg), atropine (0.1, 0.3 and 0.5 mg/kg) and alprazolam (0.08, 0.32 and 0.64 mg/kg) were administered subcutaneously 30 min before left renal artery occlusion and 6 h reperfusion. Left kidneys were processed for histological evaluations. Creatinine and BUN were measured in serum samples. Morphine, promethazine, atropine and alprazolam at all evaluated doses significantly decreased serum creatinine and BUN levels and histopathological scores. The effects of promethazine (1 mg/kg) and all doses of alprazolam were more potent than other pre‐medication drugs and doses. This study suggested a protective effect of these pre‐medication drugs on I/R injury. Although obvious studies are required, these findings may lead to effective therapies against I/R injury.     

Canine visceral leishmaniasis: Asymptomatic infected dogs as a source of L. infantum infection

Clinically infected dogs have been identified as the main reservoir hosts of visceral leishmaniasis (VL) caused by Leishmania infantum in the Mediterranean region. The objective of this study was to determine the potential of asymptomatic infected dogs compared with symptomatic ones as a source of L. infantum infection to golden hamster.For this purpose, anti-Leishmania antibodies were detected with direct agglutination test (DAT) in 13 symptomatic (7 seropositive = ≥1:320) and 53 asymptomatic (9 seropositive = ≥1:320 and 44 seronegative =  <1:320) ownership dogs. DNA of Leishmania sp. was extracted from skin and peripheral blood tissues of each dog and tested by PCR. Sixty-six Syrian golden hamsters (Mesocricetus auratus) were used for the determination of infectivity and pathogenicity of L. infantum, isolated from the dogs. We used the internal transcribed spacer 2 (ITS 2) rDNA sequence analysis. The results showed that 22 and 11 out of 66 inoculated golden hamsters were positive by PCR and parasitological examinations, respectively. From 22 PCR positive hamsters, 17 were related to asymptomatic dogs and 5 were from symptomatic ones. There was no significant difference between symptomatic and asymptomatic dogs in producing Leishmania infection in the susceptible animal model (P = 0.66). Smears and cultures of 5 dogs from 13 symptomatic dogs (38.5%) and 6 dogs from 53 asymptomatic ones (11.3%) were found to be positive at parasitological examination.All the L. infantum isolates from symptomatic and asymptomatic dogs were similar in sequencing.In conclusion, asymptomatic infected dogs as well as symptomatic ones can harbor L. infantum in their blood and skins which are virulent and infectious for inoculated golden hamster.     

The adapter proteins of TLRs,TRIF and MYD88, are upregulated in depressed individuals

Background and aims. TRIF and MYD88 are intracellular adaptor proteins for TLR signaling, and altered expression of these molecules can lead to defective or unregulated immune responses. Furthermore, previous studies revealed that depression may alter immune responses, but its mechanisms of action are unclear yet. There is a possibility that immunity and depression are linked through molecules such as TRIF and MYD88, thus, the aim of this study was to evaluate the mRNA levels of TRIF and MYD88 in the PBMCs isolated from depressed medical students. Material and methods. The current study examined 38 depressed medical students studying in Iran and 43 healthy students from the same cohort as a control group. The mRNA levels of TRIF and MYD88 were examined in parallel with a housekeeping gene using real-time PCR. Results. Our results demonstrated that expression of TRIF and MYD88 were significantly elevated in PBMCs isolated from depressed patients when compared to healthy subjects. Conclusions. Based on the current results, it seems that chronic inflammation in depressed patients correlates to the over expression of TRIF and MYD88 genes. Our results show a possible link between the reported increases of chronic inflammation in depressed individuals with unbalanced expression of genes that regulate immunity.     

The enhancement effect of beta-boswellic acid on hippocampal neurites outgrowth and branching (an in vitro study)

Increasing evidences implicate impairment of axonal integrity in mechanisms underlying neurodegenerative disorders. Beta-boswellic acid (BBA) is the major component of Boswellia serrata gum. This resin has long been used in Ayurveda (India’s traditional medicine) to prevent amnesia. In this study, the effect of BBA was examined on neurites outgrowth and branching as well as on polymerization dynamics of tubulin. The morphometric parameters (axonal length and neuritis branching) were examined microscopically after treating the hippocampal cells with BBA. Also the assembly process of tubulin was assessed using UV/V is spectrophotometer through following of absorbance at 350 nm. The results revealed that BBA could significantly enhance neurite outgrowth, branching, and tubulin polymerization dynamics. The obtained results suggest that enhancing effect of BBA on microtubule polymerization kinetics might be the origin of increasing axonal outgrowth and branching.     

Precision Nutrition Model Predicts Glucose Control of Overweight Females Following the Consumption of Potatoes High in Resistant Starch

Individual glycemic responses following dietary intake result from complex physiological processes, and can be influenced by physical properties of foods, such as increased resistant starch (RS) from starch retrogradation. Predictive equations are needed to provide personalized dietary recommendations to reduce chronic disease development. Therefore, a precision nutrition model predicting the postprandial glucose response (PPGR) in overweight women following the consumption of potatoes was formulated. Thirty overweight women participated in this randomized crossover trial. Participants consumed 250 g of hot (9.2 g RS) or cold (13.7 g RS) potatoes on two separate occasions. Baseline characteristics included demographics, 10-day dietary records, body composition, and the relative abundance (RA) and α-diversity of gut microbiota. Elastic net regression using 5-fold cross-validation predicted PPGR after potato intake. Most participants (70%) had a favorable PPGR to the cold potato. The model explained 32.2% of the variance in PPGR with the equation: 547.65 × (0 [if cold, high-RS potato], ×1, if hot, low-RS potato]) + (BMI [kg/m²] × 40.66)—(insoluble fiber [g] × 49.35) + (Bacteroides [RA] × 8.69)—(Faecalibacterium [RA] × 73.49)—(Parabacteroides [RA] × 42.08) + (α-diversity × 110.87) + 292.52. This model improves the understanding of baseline characteristics that explain interpersonal variation in PPGR following potato intake and offers a tool to optimize dietary recommendations for a commonly consumed food.     

Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site

Recent discoveries on the role of commensal microbiota have significantly changed our understanding of human physiology. The host-microbiota interplay is now an important aspect to take into account to understand immune responses and immunological diseases. Autoimmune uveitis is a sight-threatening disease that arises without a known infectious etiology. It is unknown where and how autoreactive T cells become primed to trigger disease in the eye, which is an immune privileged site. We recently reported data supporting the notion that retina-specific T cells receive a signal in the gut from commensal microbiota-derived cross-reactive antigen(s) and trigger autoimmune uveitis in the R161H mouse model. Here we discuss our published findings, as well as our recent attempts to identify the responsible microbe(s) by using different antibiotic treatments, 16S rDNA sequencing and homology searches for candidate antigenic mimic(s) of the retinal antigen.     

Local self-renewal can sustain CNS microglia maintenance and function throughout adult life

Microgliosis is a common response to multiple types of damage in the CNS. However, the origin of the cells involved in this process is still controversial and the relative importance of local expansion versus recruitment of microglia progenitors from the bloodstream is unclear. Here, we investigated the origin of microglia using chimeric animals obtained by parabiosis. We found no evidence of microglia progenitor recruitment from the circulation in denervation or CNS neurodegenerative disease, suggesting that maintenance and local expansion of microglia are solely dependent on the self-renewal of CNS resident cells in these models.